二乙酰胺三氮脒

二乙酰胺三氮脒用途

Diminazene aceturate (Diminazene diaceturate) 是一种抗锥虫药物,适用于牲畜。Diminazene aceturate 的锥虫杀虫作用的主要生化机理是通过与富含腺嘌呤-胸腺嘧啶碱基对的位点发生特异性相互作用,以非插入方式与锥虫动子体 DNA (kDNA) 结合。Diminazene aceturate 还是血管紧张素转化酶 2 (ACE2) 的激活剂,并具有强而有效的抗炎特性。

二乙酰胺三氮脒名称

[ CAS 号 ]:
908-54-3

[ 中文名 ]:
二乙酰胺三氮脒

[ 英文名 ]:
diminazene aceturate

[中文别名 ]:

[英文别名 ]:

EINECS 212-999-2
MFCD00058386
DIMINAZENE ACETURATE
Diminazene Diaceturate

二乙酰胺三氮脒生物活性

[ 描述 ]:

[ 相关类别 ]:

研究领域 >> 感染

[ 靶点 ]

Parasite[1][2]; Angiotensin-converting enzyme 2 (ACE2)[3]

[体外研究]

用去乙酰二亚胺(Berenil)预处理骨髓来源的巨噬细胞(BMDM)和树突细胞(BMDC)下调LPS-,CpG-和Poly I:C诱导的促炎细胞因子的产生,表明它可能正在影响这些分子刺激促炎细胞因子产生的共同途径。实际上,当通过流式细胞术评估时,二亚胺杂环丁酯不会改变巨噬细胞和DC上不同TLR(包括TLR2,TLR4和TLR9)的表达。相反,Diminazene aceturate显着下调MAPKs(ERK,p38和JNK),STATs(STAT1和STAT3)和NFκBp65亚基的磷酸化,这些是参与促炎细胞因子产生的关键信号分子和转录因子[2]。

[体内研究]

Diminazene aceturate(14 mg/kg；腹腔注射；雌性BALB/c小鼠和C57BL/6小鼠)治疗显着降低CD25+细胞百分比,同时降低调节性(CD4+Foxp3+)T细胞百分比并显着降低血清疾病水平加剧促炎细胞因子,包括IL-6,IL-12,TNF和IFN-γ[1]。动物模型：雌性BALB/c小鼠和C57BL/6小鼠(6-8周龄)感染T.congolense变异抗原型TC1[1]剂量：14 mg/kg给药：腹腔注射结果：显着降低百分比CD25+细胞,伴随着调节(CD4+Foxp3+)T细胞百分比的降低和显着降低血清疾病水平加剧促炎细胞因子,包括IL-6,IL-12,TNF和IFN-γ。

[参考文献]

[1]. Kuriakose S, et al. Diminazene aceturate (Berenil) modulates the host cellular and inflammatory responses to Trypanosoma congolense infection. PLoS One. 2012;7(11):e48696.

[2]. Kuriakose S, et al. Diminazene aceturate (Berenil), a new use for an old compound? Int Immunopharmacol. 2014 Aug;21(2):342-5.

[3]. Castardeli C, et al. The ACE 2 activator diminazene aceturate (DIZE) improves left ventricular diastolic dysfunction following myocardial infarction in rats. Biomed Pharmacother. 2018 Nov;107:212-218.

二乙酰胺三氮脒物理化学性质

[ 沸点 ]:
463.3ºC at 760mmHg

[ 分子式 ]:
C₂₂H₂₉N₉O₆

[ 分子量 ]:
515.52200

[ 闪点 ]:
234ºC

[ 精确质量 ]:
515.22400

[ PSA ]:
269.29000

[ LogP ]:
3.23460

[ 外观性状 ]:
固体

[ 储存条件 ]:
0-6°C

[ 稳定性 ]:
Stable. Incompatible with strong oxidizing agents.

二乙酰胺三氮脒MSDS

详细MSDS(安全技术说明书)

二乙酰胺三氮脒毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: MB7605000

CAS REGISTRY NUMBER :: 908-54-3

LAST UPDATED :: 199503

DATA ITEMS CITED :: 7

MOLECULAR FORMULA :: C14-H15-N7.2C4-H7-N-O3

MOLECULAR WEIGHT :: 515.60

WISWESSER LINE NOTATION :: MUYZR DNUNMR DYZUM &QV1MV1 2

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 663 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 258 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Mammal - species unspecified

DOSE/DURATION :: 300 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 20 mg/kg/5D-I

TOXIC EFFECTS :: Kidney, Ureter, Bladder - other changes Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - true cholinesterase Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - dehydrogenases

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 8 gm/kg

SEX/DURATION :: female 8-15 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

MUTATION DATA

TYPE OF TEST :: Micronucleus test

TEST SYSTEM :: Rodent - mouse Lymphocyte

DOSE/DURATION :: 10 umol/L

REFERENCE :: MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 300,165,1993

二乙酰胺三氮脒安全信息

[ 个人防护装备 ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ 危险品运输编码 ]:
NONH for all modes of transport

[ WGK德国 ]:
3

[ RTECS号 ]:
MB7605000

二乙酰胺三氮脒制备

以对硝基苯甲酸为原料，在高温下与对甲苯磺酰胺发生氰化反应，生成对硝基苯腈（C7H4N2O2[619-72-7]。然后由对硝基苯腈加成、胺化、还原、重氮化、偶合、成盐而得二脒那秦。1.加成、胺化将对硝基苯腈、甲醇、甲醇钠加入反应锅，搅拌溶解，在25-30℃反应3h。加入氯化铵，在10-15℃搅拌反应5h。回收甲醇至干，加入稀盐酸煮沸，过滤，得对硝基苯脒盐酸盐溶液。2.还原将上述溶液加热至50℃，加入冰醋酸，于60℃慢慢加入铁粉。加毕，升温至105℃反应5h。过滤，滤液用氢氧化钠溶液碱化至pH为12。过滤，用盐酸将滤液重新酸化至pH为1-2。浓缩，冷却结晶，过滤，得对氨基苯脒盐酸盐。3.重氮化、偶合先将一半量的对氨基苯脒盐酸盐加入水中，加盐酸溶解，于-5～0℃滴加10%的亚硝酸钠溶液，用碘化钾淀粉试纸检查终点，将另一半量的对氨基苯脒盐酸盐加少量水混匀后加入，再加饱和乙酸钠，析出黄色沉淀。过滤，滤饼溶于水中，用10%氢氧化钠溶液调节pH至9-10，析出结晶。过滤，滤饼用冷水和甲醇洗涤即得1,3-双（对脒基苯）-三氮烯。4.成盐将上述三氮烯、乙酰甘氨酸、甲醇搅拌0.5h后，用氨水调节至pH为7，升温回渡溶解。加活性炭，过滤，滤液冷却结晶。过滤、干燥，得二脒那秦。

二乙酰胺三氮脒文献

A validated and stability indicating HPLC method for analysis of diminazene aceturate and antipyrine combination in a ready injectable solution.

Drug Res. (Stuttg.) 63(6) , 300-4, (2013)

Diminazene aceturate and Antipyrine combination therapy is widely used in veterinary medicine. A simple reverse HPLC method for the analysis of samples of a ready injectable formulation containing a m...

A sensitive and reproducible in vivo imaging mouse model for evaluation of drugs against late-stage human African trypanosomiasis.

J. Antimicrob. Chemother. 70(2) , 510-7, (2015)

To optimize the Trypanosoma brucei brucei GVR35 VSL-2 bioluminescent strain as an innovative drug evaluation model for late-stage human African trypanosomiasis.An IVIS® Lumina II imaging system was us...

Inhibition of spermidine/spermine N1-acetyltransferase activity: a new therapeutic concept in rheumatoid arthritis.

Arthritis Rheumatology 66(7) , 1723-33, (2014)

Changes in polyamine-modulated factor 1 (PMF-1) promoter methylation might favor the expression of spermidine/spermine N1-acetyltransferase 1 (SSAT-1), causing excessive consumption of S-adenosyl meth...

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